All embryonic and fetal ages in this program refer to the time since fertilization.
Ages from 4 through 8 weeks are estimated to ±3 days.
Ages from 8 through 12 weeks are estimated to ±5 days.
Ages from 12 weeks through birth are generally estimated to ±1 week.
To simplify age calculations, the term “month“ assumes a 4-week period.
Age and stage conventions adopted during the embryonic period are listed in Appendix B.

English
/ .Polski [Polish]

Chapter 1 Introduction

The dynamic process by which the single-cell human zygote(zī΄gōt)[1] becomes a 100 trillion (1014) cell adult[2] is perhaps the most remarkable phenomenon in all of nature.

Researchers now know that many of the routine functions performed by the adult body become established during pregnancy – often long before birth.[3]

The developmental period before birth is increasingly understood as a time of preparation during which the developing human acquires the many structures, and practices the many skills, needed for survival after birth.

Chapter 2 Terminology

Pregnancy in humans normally lasts approximately 38 weeks[4] as measured from the time of fertilization,[5] or conception,[6] until birth.

During the first 8 weeks following fertilization, the developing human is called an embryo,[7] which means "growing within."[8] This time, called the embryonic period,[9] is characterized by the formation of most major body systems.[10]

From the completion of 8 weeks until the end of pregnancy, "the developing human is called a fetus," which means "unborn offspring." During this time, called the fetal period, the body grows larger and its systems begin to function.[11]

All embryonic and fetal ages in this program refer to the time since fertilization.[12]

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[1]Gasser, 1975, 1.[2]Guyton and Hall, 2000, 2;
Lodish et al., 2000, 12.[3]Vindla and James, 1995, 598.[4]Cunningham et al., 2001, 226;
O’Rahilly and Müller, 2001, 92.[5]O’Rahilly and Müller, 1987, 9.[6]Spraycar, 1995, 377 & 637.[7]O’Rahilly and Müller, 2001, 87.[8]
Quote from Ayto, 1990, 199.[9]
Human development during the 8-week embryonic period has been divided into a series of 23 stages called Carnegie Stages. These stages are well described in O’Rahilly and Müller, 1987. Because human growth is unique and dependent on multiple factors, different embryos may reach a certain developmental milestone or a certain size at slightly different ages. This internationally-accepted staging system provides a way to describe development independent of age and size. Each of the 23 Carnegie Stages has specific structural features. As we describe various milestones of development, the Carnegie Stage at which they occur will be noted by a designation such as: [Carnegie Stage 2]. See Appendix B for additional information relating embryonic staging and age assignments.[10]Moore and Persaud, 2003, 3.[11]
Quotes from Moore and Persaud, 2003, 3: “After the embryonic period (eight weeks), the developing human is called a fetus.“ Also see O’Rahilly and Müller, 2001, 87.[12]
This convention, termed “postfertilization age“ by O’Rahilly, has been long preferred by embryologists. [see Mall, 1918, 400;
O’Rahilly and Müller, 1999b, 39;
O’Rahilly and Müller, 2001, 88 & 91.] Obstetricians and radiologists typically assign age based on the time elapsed since the first day of the last menstrual period prior to fertilization. This is correctly termed “postmenstrual age“ and begins 2 weeks before fertilization occurs. To summarize: postmenstrual age = postfertilization age + 2 weeks. Therefore, postmenstrual age equals approximately 2 weeks at the time of fertilization. The commonly used term “gestational age“ has been used with both age conventions and is best either avoided or carefully defined with each use.

The Embryonic Period
(The First 8 Weeks)

Embryonic Development: The First 4 Weeks

Chapter 3 Fertilization

Biologically speaking, "human development begins at fertilization,"[13] when a woman and a man each combine 23 of their own chromosomes through the union of their reproductive cells.

A woman's reproductive cell is commonly called an "egg" but the correct term is oocyte (ō´ō-sīt).[14]

Likewise, a man's reproductive cell is widely known as a "sperm," but the preferred term is spermatozoon (sper´mă-tō-zō´on).[15]

Following the release of an oocyte from a woman's ovary in a process called ovulation (ov´yū-lā´shŭn),[16] the oocyte and spermatozoon join within one of the uterine tubes,[17] which are often referred to as Fallopian tubes.

The uterine tubes link a woman's ovaries to her uterus or womb.

The resulting single-celled embryo is called a zygote,[18] meaning "yoked or joined together."[19]

Chapter 4 DNA, Cell Division, and Early Pregnancy Factor (EPF)

DNA

The zygote's 46 chromosomes[20] represent the unique first edition of a new individual's complete genetic blueprint. This master plan resides in tightly coiled molecules called DNA. They contain the instructions for the development of the entire body.

DNA molecules resemble a twisted ladder known as a double helix.[21] The rungs of the ladder are made up of paired molecules, or bases, called guanine, cytosine, adenine, and thymine.

Guanine pairs only with cytosine, and adenine with thymine.[22] Each human cell contains approximately 3 billion (3×109) base pairs.[23]

The DNA of a single cell contains so much information that if it were represented in printed words, simply listing the first letter of each base would require over 1.5 million (1.5×106) pages of text![24]

If laid end-to-end, the DNA in a single human cell measures 3⅓ feet or 1 meter.[25]

If we could uncoil all of the DNA within an adult's 100 trillion (1014) cells, it would extend over 63 billion (6.3×1010) miles. This distance reaches from the earth to the sun and back 340 times.[26]

Cell Division

Approximately 24 to 30 hours after fertilization, the zygote completes its first cell division.[27] Through the process of mitosis, one cell splits into two, two into four, and so on.[28]

Early Pregnancy Factor (EPF)

As early as 24 to 48 hours after fertilization begins, pregnancy can be confirmed by detecting a hormone called "early pregnancy factor" in the mother's blood.[29]

After traveling down the uterine tube, the early embryo embeds itself into the inner wall of the mother's uterus. This process, called implantation, begins 6 days and ends 10 to 12 days after fertilization.[34]

Cells from the growing embryo begin to produce a hormone called human chorionic gonadotropin (human
kō-rē-on'ik gō'nad-ō-trō'pin), or hCG, the substance detected by most pregnancy tests.[35]

Chapter 7 The Placenta and Umbilical Cord

Following implantation, cells on the periphery of the blastocyst give rise to part of a structure called the placenta (plă-sen'tă), which serves as an interface between the maternal and embryonic circulatory systems.

The placenta delivers maternal oxygen, nutrients, hormones, and medications to the developing human; removes all waste products; and prevents maternal blood from mixing with the blood of the embryo and fetus.[37]

The placenta also produces hormones and maintains embryonic and fetal body temperature slightly above that of the mother's.[38]

The placenta communicates with the developing human through the vessels of the umbilical (ŭm-bil'i-kăl) cord.[39]

The life support capabilities of the placenta rival those of intensive care units found in modern hospitals.

Chapter 10 3 to 4 Weeks: The Folding of the Embryo

Between 3 and 4 weeks, the body plan emerges as the brain, spinal cord, and heart of the embryo are easily identified alongside the yolk sac.

Rapid growth causes folding of the relatively flat embryo.[53] This process incorporates part of the yolk sac into the lining of the digestive system and forms the chest and abdominal cavities of the developing human.[54]

Chapter 22 The Diaphragm and Intestines

The diaphragm (dī'ă-fram), the primary muscle used in breathing, is largely formed by 6 weeks.[75]

A portion of the intestine now protrudes temporarily into the umbilical cord. This normal process, called physiologic herniation (fiz-ē-ō-loj'ik
her-nē-ā'shŭn), makes room for other developing organs in the abdomen.[76]

The 8-Week Embryo

Chapter 30 8 Weeks: Brain Development

Chapter 31 Right- and Left-Handedness

By 8 weeks, 75 percent of embryos exhibit right-hand dominance. The remainder is equally divided between left-handed dominance and no preference. This is the earliest evidence of right- or left-handed behavior.[93]

Chapter 32 Rolling Over

Pediatric textbooks describe the ability to "roll over" as appearing 10 to 20 weeks after birth.[94] However, this impressive coordination is displayed much earlier in the low-gravity environment of the fluid-filled amniotic sac.[95] Only the lack of strength required to overcome the higher gravitational force outside the uterus prevents newborns from rolling over.[96]

The embryo is becoming more physically active during this time.

Motions may be slow or rapid, single or repetitive, spontaneous or reflexive.

Head rotation, neck extension, and hand-to-face contact occur more often.[97]

Twelve weeks marks the end of the first third, or trimester, of pregnancy.

Distinct taste buds now cover the inside of the mouth. By birth, taste buds will remain only on the tongue and roof of the mouth.[132]

Bowel movements begin as early as 12 weeks and continue for about 6 weeks.[133]

The material first expelled from the fetal and newborn colon is called meconium (mĭ-kō'nē-ŭm).[134] It is composed of digestive enzymes, proteins, and dead cells shed by the digestive tract.[135]

By 12 weeks, upper limb length has nearly reached its final proportion to body size. The lower limbs take longer to attain their ultimate proportions.[136]

With the exception of the back and the top of the head, the body of the entire fetus now responds to light touch.[137]

Sex-dependent developmental differences appear for the first time. For instance, female fetuses exhibit jaw movement more frequently than males.[138]

In contrast to the withdrawal response seen earlier, stimulation near the mouth now evokes a turning toward the stimulus and an opening of the mouth.[139] This response is called the "rooting reflex" and it persists after birth, helping the newborn find his or her mother's nipple during breastfeeding.[140]

The face continues to mature as fat deposits begin to fill out the cheeks[141] and tooth development begins.[142]

By 15 weeks, blood-forming stem cells arrive and multiply in the bone marrow. Most blood cell formation will occur here.[143]

Although movement begins in the 6-week embryo, a pregnant woman first senses fetal movement between 14 and 18 weeks.[144] Traditionally, this event has been called quickening.[145]

By 16 weeks, procedures involving the insertion of a needle into the abdomen of the fetus trigger a hormonal stress response releasing noradrenalin, or norepinephrin (nor-ep'i-nef'rin), into the bloodstream.[146]

In the respiratory system, the bronchial tree is now nearly complete.[147]

A protective white substance, called vernix caseosa (ver'niks
caseo'sa), now covers the fetus. Vernix protects the skin from the irritating effects of amniotic fluid.[148]

Chapter 42 5 to 6 Months (20 to 24 Weeks): Responds to Sound; Hair and Skin; Age of Viability

By 20 weeks the cochlea, which is the organ of hearing, has reached adult size[150] within the fully developed inner ear. From now on, the fetus will respond to a growing range of sounds.[151]

Hair begins to grow on the scalp.

All skin layers and structures are present, including hair follicles and glands.[152]

By 21 to 22 weeks after fertilization, the lungs gain some ability to breathe air.[153] This is considered the age of viability because survival outside the womb becomes possible for some fetuses.[154]

Chapter 42 5 to 6 Months (20 to 24 Weeks): Responds to Sound; Hair and Skin; Age of Viability

The pupils respond to light as early as 27 weeks.[163] This response regulates the amount of light reaching the retina[164] throughout life.

All components required for a functioning sense of smell are operational. Studies of premature babies reveal the ability to detect odors as early as 26 weeks after fertilization.[165]

Placing a sweet substance in the amniotic fluid increases the rate of fetal swallowing. In contrast, decreased fetal swallowing follows the introduction of a bitter substance. Altered facial expressions often follow.[166]

Through a series of step-like leg motions similar to walking, the fetus performs somersaults.[167]

The fetus appears less wrinkled as additional fat deposits form beneath the skin.[168] Fat plays a vital role in maintaining body temperature and storing energy after birth.

By 28 weeks the fetus can distinguish between high- and low-pitched sounds.[169]

By 30 weeks, breathing movements are more common and occur 30 to 40 percent of the time in an average fetus.[170]

During the last 4 months of pregnancy, the fetus displays periods of coordinated activity punctuated by periods of rest. These behavioral states reflect the ever-increasing complexity of the central nervous system.[171]

Chapter 46 9 Months to Birth (36 Weeks through Birth)

The fetus initiates labor[175] by releasing large amounts of a hormone called estrogen (es´trō-jen)[176] and thus begins the transition from fetus to newborn.

Labor is marked by powerful contractions of the uterus, resulting in childbirth.[177]

From fertilization to birth and beyond, human development is dynamic, continuous, and complex. New discoveries about this fascinating process increasingly show the vital impact of fetal development on lifelong health.

As our understanding of early human development advances, so too will our ability to enhance health––both before and after birth.

Therefore, the DNA in a single adult, if
oriented in linear fashion, would exceed 63 billion miles in length. This
is long enough to extend from the earth to the sun and
backâ€“â€“340 times.

* Approximately 25 trillionÂ red bloodÂ cellsÂ are present in the adult.[179]
It should be noted that red blood cellsÂ contain DNAÂ early in their maturation phase but this DNA degenerates and is not present in the mature form. This calculation includes the DNA from red blood cells.

There is international agreement among
embryologists that human development during the
embryonic period be divided into 23
stages (which were initially proposed by Mall, described by Streeter, and
amended by O’Rahilly and Müller in 1987).[190] These have come to be known as
Carnegie Stages. Particular
internal and external features are required for inclusion in any given
embryonic stage. These stages are independent of age and length and the
use of the term ‘stage’ should be reserved for reference to this system per O’Rahilly and
Müller in multiple publications.

Along with nearly-universal acceptance of
the human embryonic staging system, a variety of age assignments have
been proposed for each embryonic stage. Streeter believed the embryonic period spanned
a 47- to 48-day period instead of
the 56-day period accepted today. The Endowment for Human Development adopts
the convention set forth by O’Rahilly and Müller in 1987 which has received
widespread, but not universal, acceptance. O’Rahilly and Müller have since
proposed amending this convention in light of transvaginal
ultrasound data through a personal communication with Dr. Josef Wisser in 1992.[191]
These alternate proposals are provided for the interested reader.

For instance, the onset of embryonic cardiac contraction (onset
of the heartbeat) has long been
described as a Carnegie Stage 10 or possibly a
late Stage 9 event.[192] We
report this event occurring at an age of 3 weeks, 1 day (22 days) postfertilization
using the 1987 convention. Others may report this occurrence at 28 or 29 days
as shown above. Of interest is a paper by Wisser and Dirschedl who reported
using transvaginal ultrasound to visualize the embryonic heartbeat 23 days
postfertilization in two embryos fertilized in vitro “with exactly known … age“
and “in embryos from 2 mm of greatest length onwards.“[193] This finding most
closely coincides with the 1987 age convention. Schats et al. reported the
earliest cardiac activity at 25 days after
follicle aspiration in embryos conceived in vitro.[194] Tezuka et al.
reported the earliest cardiac activity at 23 days postfertilization in embryos
conceived naturally.[195]

There is considerable variation in normal
human development during the
postnatal period. The
prenatal period is no
different with variations in the size, rate of growth, and order of
appearance of some structures or functions. No one knows
the exact agerange for each
stage with absolute certainty. These approximations may change in the
future as additional knowledge is gained through careful, published research.

Hertig AT, Rock J. 1944. On the development of the early human ovum, with special reference to the trophoblast of the pre-villous stage: a description of 7 normal and 5 pathologic human ova. Am J Obstet Gynecol. 47(2):149-184.

Hertig AT, Rock J. 1945. Two human ova of the pre-villous stage, having a developmental age of about seven and nine days respectively. Carnegie Institution of Washington. Contrib Embryol. 200:67-84.

Hertig AT, Rock J. 1949. Two human ova of the pre-villous stage, having a developmental age of about eight and nine days respectively. Carnegie Institution of Washington. Contrib Embryol. 221:171-186.

O’Rahilly R, Müller F, Hutchins GM, Moore GW. 1984. Computer ranking of the sequence of appearance of 100 features of the brain and related structures in staged human embryos during the first 5 weeks of development. Am J Anat. 171(3):243-257.

O’Rahilly R, Tucker JA. 1973. The early development of the larynx in staged human embryos. Part I: Embryos of the first five weeks (to stage 15). Ann Otol Rhinol Laryngol. 82:1-27.

Streeter GL. 1945. Developmental horizons in human embryos – description of age group XIII, embryos about 4 or 5 millimeters long, and age group XIV, period of indentation of the lens vesicle. Carnegie Institution of Washington.Publ. 557. Contrib Embryol. 31(199):27-63.

Streeter GL. 1948. Developmental horizons in human embryos – description of age groups XV, XVI, XVII, and XVIII, being the third issue of a survey of the Carnegie collection. Carnegie Institution of Washington.Publ. 575.Contrib Embryol. 32(211):133-203.